Virology Journal最新文献

Reticuloendotheliosis virus (REV) is an immunosuppressive virus that can be vertically transmitted through chicken embryos. Infected chicks continuously shed the virus in their meconium and feces, facilitating horizontal transmission. Even in flocks with positive maternal antibodies, horizontal transmission can still occur. It is hypothesized that REV-associated exosomes present in the meconium of chicks mediate this horizontal transmission and immune evasion. In this study, exosomes were extracted from the meconium of chicks that tested positive for REV after the virus was experimentally introduced to chicken embryos. Through techniques including electron microscopy, genomic sequencing, and proteomic analysis, it was confirmed that these exosomes contain the complete REV genome and three major viral proteins. DF-1 cells were inoculated with REV-positive meconium exosomes, either directly or after neutralization with specific REV antibodies. In both cases, REV infection was detected in the cells via indirect immunofluorescence assay (IFA), confirming that REV-positive meconium exosomes can evade antibody neutralization and establish infection in vitro. chicks with positive maternal antibodies against REV and antibody-negative chicks were inoculated with REV. Parameters including body weight, organ somatic index, and viral replication were monitored at different time points. The results demonstrated that inoculation with REV caused severe growth retardation and hepatosplenomegaly in antibody-negative chicks. In contrast, the presence of maternal antibodies significantly attenuated the pathogenicity of the virus through neutralizing activity. However, when REV-positive meconium exosomes were inoculated to both maternal antibody-positive and antibody-negative chicks using the same protocol, no significant differences were observed in the relevant pathogenicity indicators between the two groups. This demonstrates that maternal antibodies are unable to effectively inhibit the pathogenic effects mediated by REV-positive meconium exosomes. This study characterized REV-positive meconium exosomes and demonstrated their ability to mediate effective infection both in vivo and in vitro, unaffected by antibodies. It is hypothesized that meconium exosomes represent one of the pathways through which REV achieves early horizontal transmission and immune evasion.

BK polyomavirus (BKPyV) is a human pathogen that causes severe disease in immunocompromised individuals. Although discovered in the 1970s, important gaps in our understanding of BKPyV biology persist. Key unresolved areas include the precise molecular mechanisms governing viral latency and reactivation, the specific host and viral factors determining the virus tropism towards the urinary track, and the intricate virus-host interactions that drive clinical pathogenesis. These unresolved biological questions have stalled the development of targeted therapeutics; as a result, no specific antiviral therapy is currently available for BKPyV-related diseases. In this review, we examined findings from both experimental models and clinical samples that investigate how BKPyV remodels host organelles and the molecular pathways underlying these alterations. We focus on BKPyV-driven changes in cellular membranes, including endoplasmic reticulum remodeling, mitochondrial disruption, the formation of endoplasmic reticulum-derived tubuloreticular structures, vacuoles, and autophagosomes, as well as the accumulation of lipid droplets. Collectively, these organelle-specific modifications highlight membrane remodeling as a central feature of BKPyV replication and pathogenesis. Addressing the key knowledge gaps in the molecular basis of virus-induced membrane remodeling will be critical for guiding the development of effective antiviral strategies.

Objectives: To determine the detection rate, molecular characteristics, and clinical features of enterovirus and parechovirus infections in young infants with sepsis-like illness.

Methods: A prospective study conducted from September 2023 to February 2025 at four Thai tertiary hospitals enrolled infants aged 0-3 months with sepsis-like symptoms who underwent routine laboratory tests and real-time reverse transcription polymerase chain reaction for enterovirus, human rhinovirus, and parechovirus.

Results: Of 56 infants with sepsis-like illness, 15 tested positive (26.8%; 95%CI 17.0-39.6%) for enterovirus, human rhinovirus, or parechovirus. Detected viruses included echovirus 3 and 9 (n = 3), human rhinovirus types A, B, and C (n = 8), coxsackievirus A6 and B3 (n = 2), and parechovirus type 3 (n = 2). Virus-positive infants had a higher median age than virus-negative infants (39 vs. 15 days, p = 0.004), and neonates ≤ 1 month of age were usually virus-negative (p = 0.03). Virus-positive infants older than one month were more likely to have a temperature ≥ 37.5 °C (p = 0.03). Cough was more common in virus-positive infants, while abdominal distension was more frequent in virus-negative infants (p = 0.04).

Conclusion: Enteroviruses were commonly detected in Thai infants with sepsis-like illness, with most positives attributable to enterovirus/rhinovirus group viruses, whereas parechovirus was infrequent and limited to HPeV3. Genotyping indicated established circulating lineages.

Background: Comprehensive determination of RNA structures in 5'- and 3'-terminal genomic regions across four genetically divergent coronavirus genera and thus their conservation are the first steps toward the identification of their function in coronavirus gene expression. Although these RNA structures have been experimentally analyzed for β coronaviruses, those for α coronaviruses have primarily been analyzed using bioinformatics methods. In addition, information concerning these RNA structures in γ and δ coronaviruses is limited.

Methods: To experimentally identify the conserved RNA structures in 5'- and 3'-terminal genomic regions across four coronavirus genera, the chemical probing method selective 2' hydroxyl acylation analyzed by primer extension (SHAPE) was used. Moreover, on the basis of the determined RNA structures, the potential long-range RNA‒RNA interactions and the predicted 3-dimensional (3D) RNA structures in these genomic regions were identified using RNAcanvas and RNAComposer, respectively.

Results: The results obtained were as follows: (i) the overall RNA structures in the 5'- and 3'-terminal genomic regions varied across the four coronavirus genera, as did their 3D structures; (ii) the 3'-terminal RNA structures in the representative γ coronavirus were unique among the four coronavirus genera; (iii) the stem loops (SLs) 1, 2, 4 and 5 in the 5'-termini and the SL2 and potential pseudoknot (PK) structures in the 3'-termini were the conserved RNA structures across the four coronavirus genera; and (iv) potential long-range RNA‒RNA interactions within the 5'- and 3'-terminal genomic regions can be identified.

Conclusions: The 5' and 3' terminal RNA structures in the represented α, β, γ and δ coronaviruses are analyzed and compared by using the chemical probing method SHAPE. Although different degrees of variations are found in the 5'- and 3'-terminal genomic regions across the four coronavirus genera, conserved RNA structures are identified. The determined RNA structures, the potential long-range RNA‒RNA interactions and the predicted 3D RNA structures within these genomic regions may contribute to the identification of RNA elements important for coronavirus gene expression.

Background: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a chronic disorder marked by intestinal inflammation and immune dysregulation. While bacterial dysbiosis has been widely investigated, the gut virome remains less explored. Altered viral communities, particularly bacteriophages, may destabilize microbial balance and amplify host inflammation.

Methods: To characterize virome alterations, we conducted a cross-sectional observational study in Tabriz, Iran, involving fifty participants divided into five groups: mild UC, severe UC, mild CD, severe CD, and healthy controls. Stool samples were processed for viral nucleic acid extraction and analyzed using metagenomic next-generation sequencing. Bioinformatics pipelines included diversity assessment, taxonomic profiling, functional annotation, and discriminant analysis (LEfSe). Predictive modeling was performed with random forest classifiers.

Results: Virome richness and diversity were reduced in severe UC and CD compared with controls, whereas mild cases showed values closer to healthy individuals. Taxonomic profiling revealed depletion of crAss-like phages and microviridae in IBD, along with enrichment of Caudovirales families such as siphoviridae and myoviridae. Among eukaryotic viruses, anelloviridae were prominent in severe IBD, and herpesviridae were enriched specifically in severe UC. Functional annotation highlighted enrichment of structural and lytic phage proteins in severe groups, whereas lysogeny-associated domains were more abundant in healthy controls. Random forest models based on viral features achieved appropriate accuracy, with an AUC of 0.89 for distinguishing IBD from controls and 0.83 for classifying mild versus severe disease.

Conclusion: Thus, IBD is associated with reduced virome diversity, loss of core protective phages, and selective enrichment of bacteriophages and eukaryotic viruses. These findings suggest that virome features may have potential as biomarkers for non-invasive diagnosis and severity stratification in IBD, requiring validation in larger and longitudinal cohorts.

Background: The live bird markets in the core area of the migratory bird migration base (Poyang Lake) are monitored for long-term avian influenza. The spatial and temporal patterns of avian influenza were analysed, along with the impact of the COVID-19 pandemic and vaccination.

Methods: Real-time reverse transcription polymerase chain reaction was used to test samples for general positivity of type A influenza and to detect H5, H7, and H9 subtypes to differentiate between various subtypes. The Cochran-Armitage test was applied to analyse trends in avian influenza changes, while STL and rwdrift models were used for seasonal analysis and predicting future positivity rates.

Results: A total of 2,421 avian influenza samples were collected, with a positivity rate of 75.1%. The quarterly positivity rates were all greater than 70%. Since 2016, the overall avian influenza positivity rate in urban core areas has consistently been higher than that in county seats, showing an upward trend. Among the samples, the cutting board samples had the highest positivity rate (86.7%), whereas the faecal samples had the lowest positivity rate (67.8%). The overall positivity rate of avian influenza in the post-COVID-19 period (83.0%) was significantly higher than that in the pre-COVID-19 period (65.7%). Following vaccination, the positivity rate of the H7 subtype of avian influenza virus dropped from 10.4% to 0.

Conclusions: Avian influenza positivity rate in the core areas of Poyang Lake is among the highest nationwide and exhibits seasonal patterns (higher in winter and spring). The cutting board samples had the highest positivity rate, highlighting the importance of timely cleaning of cutting boards to control the spread of avian influenza. After the COVID-19 pandemic, the avian influenza positivity rate increased significantly, with a particularly notable rise in the H5 subtype, which aligns with the global trend of increased H5 prevalence. After vaccination, the H7 subtype completely disappeared, but the impact on the H5 subtype was minimal. The predictive results indicate that avian influenza in this region will continue to rise and remain at high levels. We recommend strengthening avian influenza monitoring in this area and promptly implementing disinfection and cleaning measures in market environments to prevent future outbreaks.

Background and aims: Herpes Simplex Virus Type 1 (HSV-1) has been found to present many therapeutic challenges due to the problem of drug resistance and the low efficacy of antiviral compounds. Recently, the photocatalytic property and biocompatibility of graphitic carbon nitride (g-C₃N₄) nanosheets have been found to be promising for antiviral therapy. The antiviral efficacy and biocompatibility of the g-C₃N₄ nanosheets are assessed in this study.

Methods: g-C₃N₄ nanosheets were prepared and characterized by X-ray diffraction (XRD), Fourier Transform InfraRed Spectroscopy (FTIR), Field Emission Scanning Electron Microscopy (FESEM), and zeta potential measurements to confirm the properties. Antiviral efficacy was determined by the ability of g-C₃N₄ to block the infection of Vero cells by HSV-1 using two different methods: the virucidal assay and the post-treatment assay. The Real-Time PCR measured viral replication. The cytotoxic effect of the g-C₃N₄ nanosheets was evaluated using a neutral red uptake assay.

Results: g-C₃N₄ nanosheets exhibited a pure graphitic structure, high colloidal stability, and a porous, flake-like morphology. They achieved dose-dependent HSV-1 inhibition rates of 94.9-99.2% (virucidal) and 92.3-96.0% (post-treatment) at 600-800 µg/mL (P < 0.001). No cytotoxic effects were seen in the g-C₃N₄ nanosheets; however, increased cell viability by nearly 40% was seen when tested at a concentration of 800 µg/mL.

Conclusion: g-C₃N₄ nanosheets possess excellent biocompatibility and the ability to inhibit HSV-1 greatly, and are promising alternatives to conventional treatment regimens. There is a need to study further the mechanism of the antiviral properties of g-C₃N₄ nanosheets and the efficacy of g-C₃N₄ nanosheets in vivo.

A novel variant of the canine influenza virus H3N2 (cH3N2), designated as the M variant, was identified as containing a matrix (M) gene segment derived from the 2009 pandemic H1N1 virus (pdmH1N1), raising concerns regarding potential changes in antiviral drug sensitivity. In vitro and in vivo antiviral susceptibility assays demonstrated that while the parental cH3N2 strain was sensitive to amantadine, the M variant strain had acquired resistance to this drug. In addition, both strains remained susceptible to neuraminidase (NA) inhibitors such as oseltamivir and zanamivir. Comparative amino acid sequence analysis of the M2 protein identified a substitution, L22S, which is uniquely presented in amantadine resistant strains. Structural modeling of the M2 ion channel also suggested that the amantadine resistance observed in the M variant results from conformational alterations that impede drug binding. Collectively, these findings indicate that genetic reassortment with pdmH1N1 confers amantadine resistance in cH3N2 through the L22S substitution in the M2 protein. In addition, the preserved susceptibility to NA inhibitors suggests that these agents remain effective alternatives for controlling resistant strains, emphasizing the importance of continued molecular surveillance and diversified antiviral strategies.

Newcastle disease (ND), caused by Newcastle disease virus (NDV), is a significant threat to the poultry industry and outbreaks of virulent strains can lead to substantial economic losses. Studies to identify molecular pathways that can be used for intervention or to reduce pathology are critical for mitigating losses due to ND. In this study, we demonstrate that chicken mir-26a-5p upregulation inhibited the replication of both lentogenic and velogenic NDV strains. Computational analysis identified a highly conserved miR-26a-5p binding site in the NDV polymerase gene and transfection of the miR-26a-5p mimic following viral infection demonstrated a direct inhibition of polymerase transcripts while inhibitor transfection led to partial rescue of the miR-26a-5p mediated repression. Alternately, stable overexpression of miR-26a-5p led to the downregulation of multiple genes in the innate immune sensing pathway and led to a small but significant increase in viral titer for a velogenic NDV strain suggesting a pro-viral role. These data identified new roles for chicken miR-26a-5p in regulating NDV replication.